The expression patterns of immune response genes in the Peripheral Blood Mononuclear cells of pregnant women presenting with subclinical or clinical HEV infection are different and trimester-dependent: A whole transcriptome analysis.

Hepatitis E is an enteric disease highly prevalent in the developing countries. The basis for high mortality among pregnant hepatitis E patients remains unclear. Importantly, a large proportion of infected pregnant women present with subclinical infection as well. In order to understand the possible mechanisms influencing clinical presentation of hepatitis E in pregnant women, we explored a system biology approach. For this, PBMCs from various categories were subjected to RNAseq analysis. These included non-pregnant (NPR, acute and convalescent phases) and pregnant (PR, 2nd and 3rd trimesters, acute phase and subclinical HEV infections) patients and corresponding healthy controls. The current study deals with immune response genes. In contrast to exclusive up-regulation of nonspecific, early immune response transcripts in the NPR patients, the PR patients exhibited broader and heightened expression of genes associated with innate as well as adaptive T and B cell responses. The study identified for the first time (1) inverse relationship of immunoglobulin (Ig) genes overexpression and (2) association of differential expression of S100 series genes with disease presentation. The data suggests possible involvement of TLR4 and NOD1 in pregnant patients and alpha defensins in all patient categories suggesting a role in protection. Induction of IFNγ gene was not detected during the acute phase irrespective of pregnancy. Association of response to vitamin D, transcripts related to NK/NKT and regulatory T cells during subclinical infection are noteworthy. The data obtained here could be correlated with several studies reported earlier in hepatitis E patients suggesting utility of PBMCs as an alternate specimen. The extensive, informative data provided here for the first time should form basis for future studies that will help in understanding pathogenesis of fulminant hepatitis E.